David Juhl

Seroprevalence and incidence of hepatitis E virus infection in German blood donors

Hepatitis E virus (HEV) is transmissible by transfusion. More data are needed about seroprevalence, incidence, and viremia in blood donors for the assessment of risk of transfusion‐transmitted (TT)‐HEV infections.

The impact of donor cytomegalovirus DNA on transfusion strategies for at-risk patients

Cytomegalovirus (CMV) DNA is frequently detected in plasma of newly seropositive donors. Selection of leukoreduced blood products from donors with remote CMV infection could avoid transfusion‐transmitted CMV infections (TT‐CMV) due to primarily infected donors. However, there are no data about the prevalence of reactivations in long‐term seropositive donors compared to the incidence of window period donations in seronegative donors. Therefore, the optimal transfusion strategy for at‐risk patients is unclear.

Parvovirus B19 Infections and Blood Counts in Blood Donors

Objectives: Parvovirus B19 (B19V) is a transfusion-transmissible virus. To obtain data about the prevalence, incidence, the course of B19V infection in blood donors and whether B19V might impair their blood counts, samples from blood donors with B19V infection were investigated. Methods: Blood donations were screened for B19V DNA using the Cobas TaqScreen DPX Test® in mini-pools. B19V DNA concentration, anti-B19V IgG antibody titer and blood counts were determined in positive donors. Results: 157/23,889 (0.66%) donors provided 347 B19V DNA-positive samples. Prevalence of B19V infection was 0.45%, incidence 0.20%. B19V DNA concentrations were predominantly low; only in 8 samples were viral loads of ≥105 IU B19V DNA/ml plasma detectable. Besides a slight decrease in hemoglobin, hematocrit, mean corpuscular volume, mean cellular hemoglobin and mean hemoglobin concentration, no major differences in blood counts occurred in B19V DNA-positive samples. In samples with a low B19V DNA concentration, anti-B19V IgG titers were rather high. 98 donors provided at least 1 B19V DNA-positive follow-up sample, indicating a prolonged viremia. Conclusions: B19V infection induced no major impairment in the blood counts. In donors with low-level viremia, infectivity through their donations is probably reduced by high antibody titers. Low-level viremia is prolonged, probably exceeding 1 year in many cases.

Co-occurrence of autoantibodies in healthy blood donors

Autoimmune diseases are rare, but their incidence has increased over the past decades. Interestingly, the co‐occurrence of autoimmune diseases is well documented; however, data on the presence of more than one specific autoantibody in healthy individuals are not available. Here, we investigated the prevalence of several autoantibodies in a cohort of over 6000 healthy persons. While individual autoantibodies were rarely detected (i.e. ranging from 0.3% for ANCA to 4.6% for anti‐TPO), the cumulative prevalence of the tested autoantibodies was as high as 10%. Furthermore, our results demonstrate co‐occurrence of ANA with specific autoantibodies that target TPO, CCP and Dsg1/3, while ANCA and autoantibodies to PCA and BP180/BP230 were not more frequent in ANA‐positive compared to ANA‐negative samples. This indicates that shared and independent mechanisms influence loss of tolerance to distinct sets of self‐antigens.

Evaluation of algorithms for the diagnostic assessment and the reentry of blood donors who tested reactive for antibodies against hepatitis B core antigen

BACKGROUND: Screening of blood donations for antibodies against hepatitis B core antigen (anti‐HBc) is an accepted method to prevent some transfusion‐transmitted hepatitis B virus (HBV) infections. However, anti‐HBc testing may result in donor loss due to unspecific results in the currently available anti‐HBc tests. Algorithms to distinguish true‐positive from false‐positive results and for reentry of those donors who tested false anti‐HBc positive were evaluated retrospectively.

Coxiella burnetii - Pathogenic Agent of Q (Query) Fever

1.1.1 Structure C. burnetii is a member of the family of the Coxiellaceae bacteria and replicates intracellularly in cells of different species. Phylogenetically related bacteria include Legionellaceae, Francisellaceae, Pseudomonaceae, and other Gammaproteobacteria. Coxiella are small Gram-negative, pleomorphic, coccoid bacteria with a size of 0.2–1.0 m. They occur in 3 different forms: small cells (small cell variant, SCV) which are highly infectious, large cells (large cell variant, LCV) which develop also in cell culture, as well as spore-like particles (SLP) which are infectious and very robust to environmental conditions. Dependent on the host system, Coxiella undergoes a phase variation during growth [12]. In mammalian cells, bacteria grow as LCV, and form spore-like particles and 2 different antigenic forms described as Phase I and II.

Assignment of C1q-binding HLA antibodies as unacceptable HLA antigens avoids positive CDC-crossmatches prior to transplantation of deceased donor organs.

Soon, a virtual crossmatch shall replace the complement-dependent cytotoxicity (CDC) allocation crossmatch in the Eurotransplant region. To prevent positive CDC-crossmatches in the recipient centre, careful definition of unacceptable antigens is necessary. For highly sensitized patients, this is difficult by CDC alone. Assignment of all antibodies detected by sensitive assays, however, could prevent organ allocation. To assess the usefulness of the Luminex C1q-assay to prevent positive CDC-crossmatches, all CDC-crossmatches performed prior to deceased kidney transplantation in a 16-month-period were reviewed. Sera causing positive crossmatches were investigated by the C1q-assay. 31 out of 1432 crossmatches (2.2%) were positive. Sera involved in 26 positive crossmatches were available. C1q-binding donor-specific antibodies were detected in 19 sera (73.1%). The other sera were from recipients without any HLA antibodies detectable by CDC or common solid phase assays. Three patients had known Non-HLA antibodies causing positive CDC-results. Four crossmatches were only weak positive. Therefore, avoidance of donors with HLA antigens against whom C1q-binding antibodies were detected would have prevented all positive crossmatches due to HLA antibodies. Provided that all HLA specificities against which antibodies are detected by the Luminex C1q-assay are considered as unacceptable antigens, CDC-crossmatches prior to transplantation might safely be omitted in many patients. They should be maintained in highly immunized patients, however, for whom assignment of all C1q-positive antibodies as unacceptable antigens could lead to a significant delay or even prevention of transplantation.

Infectivity of blood products containing cytomegalovirus DNA: results of a lookback study in nonimmunocompromised patients: INFECTIVITY OF CMV DNA-POSITIVE BLOOD PRODUCTS

DNA of human cytomegalovirus (CMV) is frequently detected in plasma of donors with primary CMV infection. It is unknown, however, whether leukoreduced blood products from these donors contain sufficient amounts of infectious virus to cause transfusion‐transmitted CMV infections (TT‐CMV).

Parvovirus B19: What Is the Relevance in Transfusion Medicine?

Parvovirus B19 (B19V) has been discovered in 1975. The association with a disease was unclear in the first time after the discovery of B19V, but meanwhile, the usually droplet transmitted B19V is known as the infectious agent of the “fifth disease,” a rather harmless children’s illness. But B19V infects erythrocyte progenitor cells and thus, acute B19V infection in patients with a high erythrocyte turnover may lead to a life-threatening aplastic crisis, and acutely infected pregnant women can transmit B19V to their unborn child, resulting in a hydrops fetalis and fetal death. However, in many adults, B19V infection goes unnoticed and thus many blood donors donate blood despite the infection. The B19V infection does not impair the blood cell counts in healthy blood donors, but after the acute infection with extremely high DNA concentrations exceeding 1010 IU B19V DNA/ml plasma is resolved, B19V DNA persists in the plasma of blood donors at low levels for several years. That way, many consecutive donations that contain B19V DNA can be taken from a single donor, but the majority of blood products from donors with detectable B19V DNA seem not to be infectious for the recipients from several reasons: first, many recipients had undergone a B19V infection in the past and have formed protective antibodies. Second, B19V DNA concentration in the blood product is often too low to infect the recipient. Third, after the acute infection, the presence of B19V DNA in the donor is accompanied by presumably neutralizing antibodies which are protective also for the recipient of his blood products. Thus, transfusion-transmitted (TT-) B19V infections are very rarely reported. Moreover, in most blood donors, B19V DNA concentration is below 1,000 IU/ml plasma, and no TT-B19V infections have been found by such low-viremic donations. Cutoff for an assay for B19V DNA blood donor screening should, therefore, be approximately 1,000 IU/ml plasma, if a general screening of blood donors for single donation blood components is considered at all: for the overwhelming majority of transfusion recipients, B19V infection is not relevant as well as for the blood donors. B19V DNA screening of vulnerable patients after transfusion seems to be a more reasonable approach than general blood donor screening.

Cytomegalovirus Serostatus as Predictor for Adverse Events After Cardiac Surgery: A Prospective Observational Study

OBJECTIVE To clarify whether reactivated cytomegalovirus (CMV) infections in critically ill patients lead to worse outcome or just identify more severely ill patients. If CMV has a pathogenic role, latently infected (CMV-seropositive) patients should have worse outcome than seronegative patients because only seropositive patients can experience a CMV reactivation. DESIGN Post-hoc analysis of a prospective observational study. SETTING Single university hospital. PARTICIPANTS The study comprised 983 consecutive patients scheduled for on-pump surgery. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS CMV antibodies were analyzed in preoperative plasma samples. Postoperative adverse events (reintubation, low cardiac output or reinfarction, dialysis, stroke) and 30-day and 1-year mortality were evaluated prospectively. The plasma of reintubated patients and matched control patients was tested for CMV deoxyribonucleic acid, and 618 patients were found to be seropositive for CMV (63%). Among these, the risk for reintubation was increased (10% v 4%, p = 0.001). This increase remained significant after correction for confounding factors (odds ratio 2.70, p = 0.003) and was detectable from the third postoperative day throughout the whole postoperative period. Other outcome parameters were not different. Reintubated seropositive patients were more frequently CMV deoxyribonucleic acid-positive than were matched control patients (40% v 8%, p<0.001). CONCLUSIONS CMV-seropositive patients had an increased risk of reintubation after cardiac surgery, which was associated with reactivations of their CMV infections. Additional studies should determine whether this complication may be prevented by monitoring of latently infected patients and administering antiviral treatment for reactivated CMV infections.